The Australian Centre for Blood Diseases, Monash University, Alfred Medical Research and Educational Precinct, Melbourne, Victoria, Australia.
Lab Chip. 2017 Jul 25;17(15):2595-2608. doi: 10.1039/c7lc00498b.
Von Willebrand's disease (VWD) is the most common inherited bleeding disorder caused by either quantitative or qualitative defects of von Willebrand factor (VWF). Current tests for VWD require relatively large blood volumes, have low throughput, are time-consuming, and do not incorporate the physiologically relevant effects of haemodynamic forces. We developed a microfluidic device incorporating micro-contractions that harnesses well-defined haemodynamic strain gradients to initiate platelet aggregation in citrated whole blood. The microchannel architecture has been specifically designed to allow for continuous real-time imaging of platelet aggregation dynamics. Subjects aged ≥18 years with previously diagnosed VWD or who presented for evaluation of a bleeding disorder, where the possible diagnosis included VWD, were tested. Samples were obtained for device characterization as well as for pathology-based testing. Platelet aggregation in the microfluidic device is independent of platelet amplification loops but dependent on low-level platelet activation, GPIb/IX/V and integrin αβ engagement. Microfluidic output directly correlates with VWF antigen levels and is able to sensitively detect aggregation defects associated with VWD subtypes. Testing demonstrated a strong correlation with standard clinical laboratory-based tests. Head-to-head comparison with PFA100® demonstrated equivalent, if not improved, sensitivity for screening aggregation defects associated with VWD. This strain rate gradient microfluidic prototype has the potential to be a clinically useful, rapid and high throughput-screening tool for VWD as well as other strain-dependent platelet disorders. In addition, the microfluidic device represents a novel approach to examine the effects of high magnitude/short duration (ms) strain rate gradients on platelet function.
血管性血友病（VWD）是最常见的遗传性出血性疾病，由血管性血友病因子（VWF）的数量或质量缺陷引起。目前用于 VWD 的检测需要相对较大的血量，通量低，耗时且不包含血流动力学力的生理相关影响。我们开发了一种微流控设备，该设备结合了微收缩，利用明确的血流动力学应变梯度在柠檬酸化全血中引发血小板聚集。微通道结构经过专门设计，可连续实时成像血小板聚集动力学。年龄≥18 岁的先前诊断为 VWD 或因疑似 VWD 而就诊的患者接受了测试。对样本进行了设备特征测试以及基于病理学的测试。微流控设备中的血小板聚集与血小板放大环无关，但依赖于低水平的血小板激活、GPIb/IX/V 和整合素 αβ 结合。微流控输出与 VWF 抗原水平直接相关，并且能够灵敏地检测与 VWD 亚型相关的聚集缺陷。测试结果与标准临床实验室测试具有很强的相关性。与 PFA100®的头对头比较表明，该设备在筛查与 VWD 相关的聚集缺陷方面具有等效甚至更高的灵敏度。这种应变速率梯度微流控原型有可能成为一种临床有用的、快速且高通量的 VWD 以及其他依赖应变的血小板疾病筛查工具。此外，微流控设备代表了一种研究高幅度/短持续时间（ms）应变速率梯度对血小板功能影响的新方法。
